Preparation, hydrogen bonds, and catalytic activity in metal-promoted addition of arylboronic acids to enones of a rhodium complex containing an NHC ligand with an alcohol function

Article abstract of DOI:10.1021/om300498e

The complex RhCl(COD){3-benzyl-1-(2-hydroxy-2-phenylethyl)imidazol-2- ylidene} has been prepared by reaction of the dimer [Rh(μ-OMe)(COD)] ₂ with 3-benzyl-1-(2-hydroxy-2-phenylethyl)imidazolium chloride and characterized by X-ray diffraction analysis. The structure reveals that 75% of the molecules are associated through intermolecular O-H...Cl hydrogen bonds between the OH group of the NHC substituent of one molecule and the chloride ligand of the adjacent molecule. This complex catalyzes the addition of arylboronic acids to cyclic and acyclic enones in anhydrous toluene. The alcohol function of the substituent of the NHC ligand plays the role assigned to water in previous cases.

Full text of DOI:10.1021/om300498e

Article
pubs.acs.org/Organometallics
Preparation, Hydrogen Bonds, and Catalytic Activity in Metal-
Promoted Addition of Arylboronic Acids to Enones of a Rhodium
Complex Containing an NHC Ligand with an Alcohol Function
Itziar Penafiel,† Isidro M. Pastor,† Miguel Yus,*,† Miguel A. Esteruelas,*,‡ and Montserrat Olivan‡
́
̃
†
́
́
Departamento de Quımica Organ
99, 03080 Alicante, Spain
́
ica, Facultad de Ciencias and Instituto de Sıntesis Organ
́
ica (ISO), Universidad de Alicante, Apdo.
‡
́
́
Departamento de Quımica Inorganica-Instituto de Sıntesis Química y Catalisis Homogenea (ISQCH), Universidad de
Zaragoza-CSIC, 50009 Zaragoza, Spain
́
́
́
S
* Supporting Information
ABSTRACT: The complex RhCl(COD){3-benzyl-1-(2-hydroxy-2-
phenylethyl)imidazol-2-ylidene} has been prepared by reaction of the
dimer [Rh(μ-OMe)(COD)]2 with 3-benzyl-1-(2-hydroxy-2-phenylethyl)-
imidazolium chloride and characterized by X-ray diffraction analysis. The
structure reveals that 75% of the molecules are associated through
intermolecular O−H···Cl hydrogen bonds between the OH group of the
NHC substituent of one molecule and the chloride ligand of the adjacent molecule. This complex catalyzes the addition of
arylboronic acids to cyclic and acyclic enones in anhydrous toluene. The alcohol function of the substituent of the NHC ligand
plays the role assigned to water in previous cases.
bearing acidic substituents, such as alcohols, at the N center
constitutes a special challenge.
INTRODUCTION
■
The chemistry of N-heterocyclic carbenes (NHCs) is a field of
great current interest due to the transversal applications of the
NHC complexes, including homogeneous catalysis,1 antimicro-
bial and cytotoxic agents,2 photoactive sites in luminescent
materials for self-assembly into liquid crystalline materials and
metallosupramolecular structures, and synthons for molecular
switches and conducting polymeric materials.3 Although several
methods have been developed for the preparation of complexes
containing these ligands, deprotonation of imidazolium salts is
the most used synthetic pathway.4
The vast majority of reported NHC ligands are substituted at
nitrogens by alkyl or aryl groups. Imidazolium salts with
carbonyl,5 pyridyl,6 pyrazolyl,7 amine,8 and phosphine9
substituents are also known. They can be deprotonated and
are thus suitable for the preparation of metal complexes.
The catalytic transformations usually take place at the metal
center. However, there is an increasing number of reactions
involving both the metal center and an acidic hydrogen atom of
the ligands,10 which can further form hydrogen bonds. It has
been found that processes involving passive diffusion depend
primarily on the hydrogen-bonding capacity or polar surface
area of a drug solute.11 Intermolecular hydrogen bonds also
play an important role in the design and engineering of
architectures of many polymeric materials. Hydrogen bonding
can affect the chain length, chain packing, rigidity, and
molecular order.12 In addition, the induction and stabilization
of liquid crystallinity by hydrogen bonding has been shown.13
As a consequence of these observations, the preparation of
transition-metal complexes with N-heterocyclic carbenes
Alcohol-functionalized imidazolium salts are readily acces-
sible by the nucleophilic opening of epoxides.14 However,
alcohol-functionalized imidazolylidene transition-metal com-
plexes are scarce.15 In order to justify this, it has been argued
that the alcohol function is more acidic than the heterocycle.
Thus, the single deprotonation leads to zwitterionic alcoholate
imidazolium derivatives.16
The hexahydride complex OsH6(PiPr3)2 is basic enough to
produce the deprotonation of imidazolium salts, generating
families of osmium polyhydride derivatives containing both
normal and abnormal imidazolylidene complexes.6e,17 Further-
more, it shows a marked tendency to dehydrogenate alcohols.18
In agreement with both properties, the hexahydride reacts with
alcohol-functionalized imidazolium salts to give NHC-keto
derivatives.19 In the search for new transition-metal compounds
with NHC ligands bearing an alcohol function, we are
investigating the use of basic transition-metal precursors
without capacity for dehydrogenating alcohols. Thus, we have
recently reported that the reaction of Pd(OAc)2 with 3-benzyl-
1-(2-hydroxy-2-phenylethyl)imidazolium chloride affords trans-
PdCl2{3-benzyl-1-(2-hydroxy-2-phenylethyl)imidazol-2-yli-
dene}2, which is an efficient catalyst for the Hiyama cross-
coupling reaction between arylsiloxanes and aryl halides.20
Now, we show that the dimer [Rh(μ-OMe)(COD)]2 affords a
related rhodium derivative, which catalyzes the 1,4-addition of
arylboronic acids to enones, in the absence of water.
Received: June 5, 2012
Published: August 15, 2012
© 2012 American Chemical Society
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C(23), C(24) and C(19), C(20) are increased to 1.387(9) and
1.336(12) Å, respectively. An extended view of the structure
(Figure 2) reveals that 75% of the molecules of complex are
RESULTS AND DISCUSSION
■
1. Preparation and Characterization of the Hydrox-
yalkyl-Functionalized NHC-Rh Complex. Treatment of
[Rh(μ-OMe)(COD)]2 (1) with 2.0 equiv of 3-benzyl-1-(2-
hydroxy-2-phenylethyl)imidazolium chloride in acetone, at
room temperature, for 3 h leads to RhCl(COD){3-benzyl-1-
(2-hydroxy-2-phenylethyl)imidazol-2-ylidene} (2) as a result of
the selective deprotonation of the imidazolium ring in the
presence of the alcohol function, the release of methanol from
the metal centers, and the coordination of the resulting
hydroxyalkyl-functionalized NHC ligand and the chloride anion
to the rhodium atoms of 1. Complex 2 was isolated as a yellow
solid in 75% yield, according to eq 1.
Figure 2. View of the intermolecular interactions via hydrogen
bonding in the structure of complex 2. Symmetry codes: (I) −1/2 + x,
1
1
1
1
1/2 + y, /2 + z; (II) /2 + x, /2 − y, /2 + z; (III) −1 + x, y, −1 + z;
(IV) 1 + x, y, 1 + z.
associated through intermolecular O−H···Cl hydrogen bonds
between the OH group of one molecule and the chloride ligand
of the adjacent molecule. In agreement with this, the separation
H(1A)−Cl(1) of 2.449(2) Å is shorther than the sum of the
van der Waals radii of hydrogen and chloride (rvdw(H) = 1.20
Å, rvdw(Cl) = 1.75 Å).22 Furthermore, the O(1A)···Cl(1)
separation is 3.263(6) Å and the angle O(1A)−H(1A)−Cl(1)
is almost linear at 163.3(5)°. The remaining 25% of the
molecules form an intramolecular O(1B)−H(1B)−Cl(1)
hydrogen bond with H(1B)···Cl(1) and O(1B)−Cl(1)
separations of 2.004(3) and 2.83(2) Å, respectively, and an
O(1B)−H(1B)−Cl(1) angle of 179.11(4)°.
Complex 2 has been characterized by X-ray diffraction
analysis. Figure 1 gives a view of the structure. The
1
The H and 13C{1H} NMR spectra reveal that in solution
complex 2 exists as a 63:37 mixture of the two pairs of
diastereoisomers, resulting from the chirality of C(5) and the
fact that the molecular square plane is not a symmetry plane:
i.e., as a mixture of S,Ra and S,Sa along with their respective
enantiomers R,Sa and R,Ra. The 63:37 mixture of the pair of
diastereoisomers R,Ra and R,Sa was prepared by the reaction of
1 with (R)-3-benzyl-1-(2-hydroxy-2-phenylethyl)imidazolium
chloride as shown in eq 1. As expected for the presence of an
1
alcohol function in the NHC ligand, the H NMR spectra of
the mixtures contain two OH resonances at 3.88 (major) and
4.31 ppm (minor). In agreement with the presence of four
inequivalent C(sp2) atoms in the coordinated olefin, the
13C{1H} NMR spectra show four olefin resonances at 67.8,
69.8, 98.3, and 98.5 ppm for the major diastereoisomer and
three signals at 69.3 (two carbons), 98.8, and 99.4 ppm for the
minor species. The NHC Rh−C resonances appear at 182.2
(major) and 183.4 ppm (minor), as doublets with Rh−C
coupling constants of 50.5 and 51.0 Hz, respectively.
2. Addition of Organoborons to α,β-Unsaturated
Ketones. The rhodium-catalyzed conjugated addition of
organoboron reagents to α,β-unsaturated carbonyl compounds
is paramount in organic chemistry.23 This reaction is generally
performed in the presence of water, which appears to have two
functions:24 to hydrolyze the enolate intermediate that
generates the addition product and to facilitate the trans-
metalation from the organoboron compound to the metal
center through a hydroxorhodium intermediate. With the well-
established complex 2 in hand, we reasoned that the alcohol
function of the NHC ligand could perform the roles of the
water, and in this way, the reaction should work in anhydrous
solvent.
Figure 1. Molecular diagram of complex 2. Selected bond lengths (Å)
and angles (deg): Rh−Cl(1) = 2.3795(19), Rh−C(1) = 2.004(9),
Rh−C(19) = 2.167(12), Rh−C(20) = 2.174(7), Rh−C(23) =
2.134(6), Rh−C(24) = 2.095(7), C(19)−C(20) = 1.336(12),
C(23)−C(24) = 1.387(9); Cl(1)−Rh-C(1) = 89.6(2).
coordination geometry around the rhodium atom is almost
square planar with the imidazolylidene ring perpendicular to
the coordination plane, forming a dihedral angle of 89.20°. The
greatest deviation from the best plane through the Rh, Cl(1),
and C(1) atoms and the midpoints of the coordinated C−C
double bonds of the diene is 0.0051 Å for the metal. The Rh−
C(1) bond length of 2.004(9) Å compares well with those
reported for other Rh-NHC complexes.21 Due to the different
trans influences of the NHC and the chloride ligands, a slight
difference in the rhodium to carbon distances of the
coordinated olefin is observed. While the carbon atoms
C(23) and C(24) (trans to Cl(1)) are located at 2.134(6)
and 2.095(7) Å from the metal center, the Rh−C bond lengths
for C(19) and C(20) (trans to C(1)) are 2.167(12) and
2.174(7) Å. As expected, owing to the coordination to the
metal center, the distances between the sp2 carbon atoms
The addition of phenylboronic acid (3a) to cyclohex-2-enone
(4) in the presence of 1 mol % of 2 was chosen in order to
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study the optimal reaction conditions.25 Thus, a design of
experiments (DOE) was used to plan a minimum set of assays
to check the maximum range of variables that would determine
the maximum information about which were the critical factors
and what was the best combination of variables to obtain the
highest yield of 3-phenylcyclohexanone (5a). The DOE was
performed for five parameters with an average of two levels
each. They were as follows: (i) temperature, (ii) the use of
cycloocta-1,5-diene as additive, (iii) base, (iv) solvent, and (v)
conventional heating (6 h) versus microwave heating (1 h).
The selection of experiments was carried out according to a
Taguchi L15 array. Table 1 collects the obtained results. The
Scheme 1
Table 1. Addition of Phenylboronic Acid to Cyclohex-2-
enone
temp
(°C)
yield
a
heating
additive solvent
base
(%)
conventional 6 h
conventional 6 h
conventional 6 h
conventional 6 h
MW 1 h
40
40
40
60
60
40
60
60
40
60
60
60
60
60
60
none
none
none
COD
COD
none
none
none
none
none
none
COD
none
COD
none
toluene
water
NaOH
none
KOH
none
none
none
none
none
none
none
none
none
NaOH
none
NaOH
80
68
8
THF
toluene
THF
98
42
53
86
75
0
conventional 6 h
conventional 6 h
conventional 6 h
MW 1 h
toluene
toluene
water
water
MW 1 h
water
23
14
95
78
80
48
MW 1 h
toluene
toluene
toluene
water
conventional 6 h
conventional 6 h
conventional 6 h
conventional 6 h
B(OH)]n in C6D12 at 70 °C.28 The subsequent coordination of
the α,β-unsaturated ketone to the rhodium atom, followed by
the regioselective 1,4-insertion of the coordinated substrate into
the Rh−Ar bond of 7, should lead to 8 via oxallyl or
hydroxoallyl intermediates.29 Thus, the intramolecular proto-
nolysis of the alcoholated group of 8 by the alcohol substituent
of the NHC ligand could afford the catalytic product and 9,
containing a chelate NHC-alcoholate group, which should
regenerate the boronate 6 by reaction with the arylboronic acid.
The role of the hydroxyl group is strongly supported by the fact
that the complex RhCl(COD){3-benzyl-1-(2-phenylethyl)-
imidazol-2-ylidene}, which does not bear an alcohol function,
does not catalyze the reaction under anhydrous conditions,
while 5a is formed in 78% yield, after 6 h, in the presence of an
aqueous 2.5 M NaOH solution.
water
a
The yield was calculated by GLC analysis by employing tridecane as
an internal standard.
reaction is better performed at 60 °C by conventional heating
in anhydrous toluene and in the presence of cycloocta-1,5-diene
as an additive. Under these conditions, 5a is obtained in 96%
isolated yield (eq 2).
The presence of free cycloocta-1,5-diene during the catalysis
prevents the dissociation of the coordinated olefin, increasing
the stability of the catalytic system and the yield of the reaction
(Figure 3a). The reaction works well in the absence of base.
However, in the presence of 1.0 equiv of NaOH, the
reproducibility of the assays is better (Figure 3b). This appears
to be related to the neutralization of the generated HCl during
the activation of the catalytic precursor, which could degrade
the catalyst and/or the substrate.30
The versatility of the catalyst has been corroborated by using
a variety of arylboronic acids (3a−g) bearing electron-donating
and electron-withdrawing groups (Table 2). The addition of 1-
naphthylboronic acid to cyclohexen-2-one gives the expected
product 5b in good yield, both in the presence and in the
absence of NaOH. The corresponding 3-substituted cyclo-
hexanones 5c−g are also obtained in high yields. No reaction
was observed when employing a more congested boron
derivative such as 2,6-dimethoxyphenylboronic acid. The use
The reaction certainly works in the absence of water, in
agreement with our initial hypothesis. Thus, 5a is also formed
by using triphenylboroxine instead of phenylboronic acid,26
although the bigger steric hindrance of the boroxine gives rise
to a slower reaction (24% conversion after 6 h). On the basis of
the Hayashi mechanism,24a,b this fact can be rationalized
according to Scheme 1. The catalytically active species is
generated by transmetalation from the organoboron com-
pound.23c,27 Thus, the reaction of 2 with the arylboronic acid
should give the boronate 6 and HCl. Then the key intermediate
6 could undergo intramolecular transfer of the aryl group from
boron to rhodium to afford the square-planar aryl species 7, by
a β-aryl elimination pathway. In this context, it should be noted
that Hartwig and co-workers have previously reported that the
silylamido precursor Rh[N(SiMe3)2](PEt3)2 reacts with
arylboronic acids, in the presence of PEt3, to yield Rh[OB-
(OH)Ph](PEt3)3, which evolves into Rh(Ar)(PEt3)3 and [O
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Figure 3. (a) Boxplot of experimental data with and without additive. (b) Boxplot of experimental data with and without base.
Table 2. Conjugate Addition of Arylboronic Acids to
Cyclohex-2-enone
Table 3). The addition of phenylboronic acid in the absence of
NaOH gives 4-phenylbutan-2-one (13a) as the only addition
a
Table 3. Conjugate Addition of Arylboronic Acids to Methyl
a
Vinyl Ketone
b
c
entry
Ar
boronic acid
base
product yield (%)
1
Ph
3a
3b
3b
3c
3c
3d
3d
3e
3f
none
5a
5b
5b
5c
5c
5d
5d
5e
5f
96
89
86
77
89
57
88
92
53
64
74
2
1-naphthyl
none
b
3
1-naphthyl
NaOH
none
entry
Ar
boronic acid
product
yield (%)
4
4-(CF3)C6H4
4-(CF3)C6H4
4-BrC6H4
1
2
3
4
5
Ph
3a
3b
3c
3d
3e
13a
13b
13c
13d
13e
89
84
66
70
80
5
NaOH
none
1-naphthyl
6
4-(CF3)C6H4
4-BrC6H4
7
4-BrC6H4
NaOH
NaOH
none
8
4-(MeO)C6H4
2-MeC6H4
4-(MeO)C6H4
9
a
Reaction performed with methyl vinyl ketone (0.5 mmol) and
10
11
12
2-MeC6H4
3f
NaOH
NaOH
NaOH
5f
arylboronic acid (0.4 mmol) in the presence of complex 2 (0.005
mmol), cycloocta-1,5-diene (0.075 mmol), and NaOH (0.2 mL, 2.5 M
aqueous solution) at 60 °C in a sealed tube with toluene over 6 h.
3-ClC6H4
3g
3h
5g
5h
2,6-(MeO)2C6H3
a
b
Reaction performed with cyclohex-2-enone (0.5 mmol) and
Isolated yield of pure product after purification by chromatography
arylboronic acid (0.7 mmol) in the presence of complex 2 (0.005
(preparative TLC, hexane/ethyl acetate mixtures).
mmol) and cycloocta-1,5-diene (0.075 mmol), at 60 °C in toluene
b
over 6 h. The reaction was performed in the absence of a base or with
c
NaOH (0.2 mL, 2.5 M aqueous solution). Isolated yield of pure
product after purification by chromatography (preparative TLC,
hexane/ethyl acetate mixtures).
product detected by GC. The amount of saturated ketone
isolated after the disappearance of the substrate is, however,
lower than 59%. The presence of 1.0 equiv of NaOH during the
catalysis increases the isolated yield to 89%. This is consistent
with the neutralization of the HCl generated in the formation
of 6, which prevents the partial subtraction of the substrate as a
nondetected polymer. The polymerization of methyl vinyl
ketone promoted by H+ is a well-known process. In the
presence of NaOH, 1-naphthyl- and 4-methoxyphenyl boronic
acids give the corresponding products 13b,e with yields over
80%, whereas the use of boron reagents with electron-
withdrawing groups such as 4-trifluoromethylphenyl- and 4-
bromophenylboronic acids produces the expected compounds
13c,d in 66% and 70% yields, respectively.
of the 63:37 mixture of the pair of diastereoisomers R,Ra and
R,Sa produces the expected products 5 with similar yields and
enantioselectivities of about 10%. Additionally, it should be
mentioned that the addition of 3a to cyclohepten-2-one (10) is
less effective than the addition to cyclohexen-2-one. Thus,
under basic conditions, 3-phenylcycloheptanone (11) is only
isolated in 64% yield (eq 3).
CONCLUDING REMARKS
■
The complex RhCl(COD){3-benzyl-1-(2-hydroxy-2-
phenylethyl)imidazol-2-ylidene}, bearing an alcohol function,
has been prepared by direct metalation of 3-benzyl-1-(2-
hydroxy-2-phenylethyl)imidazolium chloride with the dimer
[Rh(μ-OMe)(COD)]2. In the solid state, 75% of the molecules
of the complex are associated through intermolecular O−H···Cl
hydrogen bonds between the OH group of one molecule and
the chloride ligand of the adjacent molecule. In anhydrous
toluene, it catalyzes the addition of arylboronic acids to cyclic
and acyclic enones. The alcohol substituent of the NHC ligand
Complex 2 also catalyzes the addition of arylboronic acids to
acyclic enones such as methyl vinyl ketone (12 in eq 4 and
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67.8 (d, JRh−C = 14.6, CH COD), 59.0 (s, −CH2−), 54.8 (s,
−CH2−), 33.6, 33.0, 29.6, 28.7 (all s, −CH2− COD).
appears to play the role assigned to water in this interesting
reaction.
1
Minor Diastereoisomer. H NMR (300 MHz, CD2Cl2, 293K, plus
COSY): δ 7.62−7.34 (m, 10H, Ph), 7.03 (d, JH−H = 1.8, 1H, CH im),
EXPERIMENTAL SECTION
6.79 (d, JH−H = 1.8, 1H, CH im), 6.58 (m, 1H, −CH(OH)−), 5.81
■
(AB spin system, JA‑B = 15, Δν = 127, 2H, −CH2Ph), 5.35 (dd, JH−H
=
General Information. The organometallic syntheses were carried
out with rigorous exclusion of air using Schlenk-tube techniques.
Solvents (except for acetone, which was dried and distilled under
argon) were obtained oxygen- and water-free from an MBraun solvent
10.5, JH−H = 13.8, 1H, −CH2CH(OH)−), 5.07−4.95 (m, 3H, 2 CH
COD + −CH(OH)−), 4.32 (dd, JH−H = 13.8, JH−H = 3.4, 1H,
−CH2CH(OH)−), 4.31 (br, 1H, -OH), 3.45−3.32 (m, 2H, CH
COD), 2.46−1.91 (m, 8H, CH2 COD). 13C{1H} NMR (100.62 MHz,
CD2Cl2, 293 K, plus apt): δ 183.4 (d, JRh−C = 51, Rh−C), 142.7, 136.9
(both s, Cipso Ph), 129.1, 128.9, 128.4, 128.2, 127.9, 126.5 (all s, CH
Ph), 121.7, 121.4 (both s, CH im), 99.4 (d, JRh−C = 6.8, CH COD),
98.8 (d, JRh−C = 6.9, CH COD), 73.9 (s, −CH(OH)−), 69.3 (d,
JRh−C = 14.5, CH COD), 58.5 (s, −CH2−), 55.5 (s, −CH2−), 33.2,
33.1, 29.3, 29.0 (all s, −CH2− COD).
1
purification apparatus. H and 13C{1H} NMR spectra were recorded
on Bruker 300 ARX, Bruker Avance 300 MHz, and Bruker Avance 400
MHz instruments. Chemical shifts (expressed in parts per million) are
referenced to residual solvent peaks. Coupling constants J are given in
hertz. Infrared spectra were recorded on 400D, Jasco 4100LE (Pike
MIRacle ATR), and Perkin-Elmer Spectrum 100 spectrophotometers.
C, H, and N analyses were carried out in a Perkin-Elmer 2400 CHNS/
O analyzer. High-resolution electrospray mass spectra were acquired
using a MicroTOF-Q hybrid quadrupole time-of-flight spectrometer
(Bruker Daltonics, Bremen, Germany). Mass spectra (EI) were
obtained at 70 eV on an Agilent 5973 spectrometer; fragment ions are
Preparation of RhCl(COD){(R)-3-benzyl-1-(2-hydroxy-2-
phenylethyl)imidazol-2-ylidene} (2). A mixture of [Rh(μ-OMe)-
(COD)]2 (1; 100 mg, 0.206 mmol) and (R)-3-benzyl-1-(2-hydroxy-2-
phenylethyl)imidazolium chloride (130 mg, 0.413 mmol) was
dissolved in acetone (5 mL). The reaction mixture was stirred at
room temperature for 3 h, during which time the formation of a yellow
precipitate was observed. The yellow solid thus formed was washed
given in m/z units with relative intensities (%) in parentheses. [Rh(μ-
31
OMe)(COD)]2
and 3-benzyl-1-(2-hydroxy-2-phenylethyl)-
imidazolium chloride19 were prepared by published methods. All
commercially available reagents (Acros, Aldrich, Fluka) were used
without further purification. Melting points were determined with a
Reichert Thermovar hot plate apparatus and are uncorrected.
Analytical TLC was performed on Merck aluminum sheets with silica
gel 60 F254. Silica gel 60 (0.04−0.06 mm) was employed for flash
chromatography.
1
with acetone and dried in vacuo. Yield: 125 mg (58%). H NMR
spectroscopy show the presence of a pair of diastereoisomers in the
ratio 63:37.
Preparation of RhCl(COD){3-benzyl-1-(2-phenylethyl)-
imidazol-2-ylidene}. A mixture of [Rh(μ-OMe)(COD)]2 (1; 100
mg, 0.206 mmol) and 3-benzyl-1-(2-phenylethyl)imidazolium chloride
(123 mg, 0.413 mmol) was dissolved in acetone (5 mL). The reaction
mixture was stirred at room temperature for 5 h, during which time the
formation of a yellow precipitate was observed. The yellow solid thus
formed was washed with acetone and dried in vacuo. Yield: 148 mg
(72%). Anal. Calcd for C26H31ClN2Rh: C, 61.24; H, 6.13; N, 5.49.
Found: C, 60.85; H, 5.77; N, 5.12. IR (cm−1): ν(CC) 1602 (d).
HRMS (electrospray, m/z): calcd for C26H31N2Rh [M − Cl]+
Preparation of 3-Benzyl-1-(2-phenylethyl)imidazolium
Chloride. 1-Chloro-2-phenylethane (5.5 mmol, 0.75 mL) was added
at room temperature to a solution of 1-benzylimidazole (5 mmol, 0.79
g) in acetonitrile (10 mL), and the resulting mixture was stirred at 85
°C for 16 h, in a sealed tube. The solution was concentrated to
dryness, and diethyl ether was added to the residue to afford a yellow
oil. The mixture was sonicated for 15 min, and the ethereal phase was
1
473.1459; found 489.1512. H NMR (300 MHz, CD2Cl2, 293 K): δ
1
decanted. The product was dried in vacuo. Yield: 0.94 g (63%). H
7.42−7.25 (m, 10H, Ph), 6.72 (d, JH−H = 2, 1H, CH im), 6.55 (d, JH−H
= 2, 1H, CH im), 5.77 (AB spin system, JA‑B = 14.8, Δν = 105, 2H,
−CH2Ph), 5.10−4.98 (m, 2H, CH COD), 4.89 (ddd, JH−H = 15,
NMR (400 MHz, CDCl3, 293 K): δ 9.63 (s, 1H), 7.36−7.30 (m, 6H),
7.28−7.27 (m, 1H), 7.22−7.20 (m, 3H), 7.14−7.12 (m, 2H), 5.43 (s,
2H), 4.58 (t, JH−H = 7.0, 2H), 3.19 (t, JH−H = 7.0, 2H). 13C{1H} NMR
(75 MHz, CDCl3, 293 K): δ 136.2, 135.1, 132.9, 129.2, 128.8, 128.6,
127.1, 122.5, 121.7, 53.1, 51.0, 36.1. MS: m/z (%) 263 (M+ − Cl, 2),
261 (7), 173 (7), 172 (60), 105 (9), 104 (15), 103 (7), 92 (11), 91
(100), 81 (35), 65 (17).
JH−H = 9.5, JH−H = 5, 1H, −CH2CH2Ph), 4.57 (ddd, JH−H = 15, JH−H
=
9, JH−H = 7.6, 1H, −CH2CH2Ph), 3.41 (ddd, JH−H = 13.5, JH−H = 5,
JH−H = 9, 1H, −CH2CH2Ph), 3.35−3.28 (m, 2H, CH COD), 3.41
(ddd, JH−H = 13.5, JH−H = 9.5, JH−H = 7.6, 1H, −CH2CH2Ph), 2.38−
2.28 (m, 4H, CH2 COD), 1.98−1.83 (m, 4H, CH2 COD). 13C{1H}
Preparation of RhCl(COD){3-benzyl-1-(2-hydroxy-2-
phenylethyl)imidazol-2-ylidene} (2). A mixture of [Rh(μ-OMe)-
(COD)]2 (1; 100 mg, 0.206 mmol) and 3-benzyl-1-(2-hydroxy-2-
phenylethyl)imidazolium chloride (130 mg, 0.413 mmol) was
dissolved in acetone (5 mL). The reaction mixture was stirred at
room temperature for 3 h, during which time the formation of a yellow
precipitate was observed. The yellow solid thus formed was washed
with acetone and dried in vacuo. Yield: 162 mg (75%). Anal. Calcd for
C26H30ClN2ORh: C, 59.33; H, 5.77; N, 5.34. Found: C, 59.65; H,
5.36; N, 5.00. IR (cm−1): ν(O−H) 3406 (w); ν(C−O) 1099 (m).
HRMS (electrospray, m/z): calcd for C26H30N2ORh [M − Cl]+
489.1408; found 489.1455. 1H and 13C{1H} NMR spectroscopy
shows the presence of two pairs of diastereoisomers in the ratio 63:37.
NMR (100.62 MHz, CD2Cl2, 293 K, plus apt): δ 183.2 (d, JRh−C
=
50.5, Rh−C), 138.9, 137.1 (both s, Cipso Ph), 129.4, 129.1, 129.0,
128.6, 128.4, 127.0 (all s, CH Ph), 121.6, 120.7 (both s, CH im), 98.2
(d, JRh−C = 6.9, CH COD), 98.0 (d, JRh−C = 6.9, CH COD), 70.0
(d, JRh−C = 14.4, CH COD), 69.3 (d, JRh−C = 14.4, CH COD),
54.8 (s, NCH2Ph), 52.8 (s, NCH2CH2Ph), 34.5 (s, NCH2CH2Ph),
33.3, 32.8, 29.7, 29.1 (all s, −CH2− COD).
General Procedure for the Conjugate Addition of Arylbor-
onic Acids to Enones. In a 10 mL vessel containing a solution of
complex 2 (0.005 mmol, 2.62 mg) and the corresponding arylboronic
acid (0.7 mmol) in toluene (1 mL), the enone (0.5 mmol) and
cycloocta-1,5-diene (0.075 mmol, 9.2 μL) were added. Then, if
necessary, 0.2 mL of an aqueous solution of NaOH (2.5 M) was added
dropwise. The vessel was sealed with a septum, and the mixture was
heated at 60 °C for 6 h. The reaction mixture was hydrolyzed at room
temperature with H2O (5 mL). The organic phase was separated, and
the resulting aqueous layer was extracted with Et2O (3 × 5 mL). The
combined organic phases were filtered over a plug of Celite and silica,
dried over anhydrous MgSO4, concentrated under reduced pressure,
and purified by chromatography (preparative TLC plates, hexane/
ethyl acetate) to give the corresponding final products 5 and 13. Yields
are given in Tables 2 and 3.
1
Major Diastereoisomer. H NMR (300 MHz, CD2Cl2, 293 K): δ
7.62−7.34 (m, 10H, Ph), 6.78 (d, JH−H = 2.1, 1H, CH im), 6.68 (d,
JH−H = 2.1, 1H, CH im), 6.58 (m, 1H, −CH(OH)−), 5.87 (AB spin
system, JA‑B = 15, Δν = 58, 2H, −CH2Ph), 5.07−4.95 (m, 2H, CH
COD), 4.86 (dd, JH−H = 13.5, JH−H = 3.1, 1H, −CH2CH(OH)−), 3.94
(dd, JH−H = 13.5, JH−H = 9.6, 1H, −CH2CH(OH)−), 3.88 (d, JH−H
=
4.8, 1H, −OH), 3.45−3.32 (m, 2H, CH COD), 2.46−1.91 (m, 8H,
CH2 COD). 13C{1H} NMR (100.62 MHz, CD2Cl2, 293 K, plus apt):
δ 182.2 (d, JRh−C = 50.5, Rh−C), 142.3, 137.0 (both s, Cipso Ph), 129.1,
128.8, 128.5, 128.4, 128.2, 126.1 (all s, CH Ph), 124.4, 120.0 (both s,
CH im), 98.5 (d, JRh−C = 6.9, CH COD), 98.3 (d, JRh−C = 7.0, CH
COD), 72.3 (s, −CH(OH)−), 69.8 (d, JRh−C = 14.6, CH COD),
Physical and Spectroscopic Data of the Addition Products.
3-Phenylcyclohexanone (5a).32 Yellow oil. 1H NMR (400 MHz,
CDCl3): δ 7.39−7.34 (m, 2H), 7.28−7.24 (m, 3H), 3.06−2.95 (m,
6158
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Organometallics
Article
1H), 2.59−2.37 (m, 2H), 2.16−2.06 (m, 2H), 1.92−1.73 (m, 1H). 13
C
199 (12) [M+], 198 (75), 155 (66), 154 (13), 153 (22), 152 (15), 142
(12), 141 (100), 128 (21), 115 (24).
NMR (100 MHz, CDCl3): δ 210.9, 144.6, 128.6, 126.6, 126.5, 48.9,
44.7, 41.1, 32.7, 25.5. MS: m/z (%) 174 (46) [M+], 131 (74), 118
(27), 117 (91), 115 (20), 105 (16), 104 (70), 103 (26), 91 (31).
4-[4-(Trifluoromethyl)phenyl]butan-2-one (13c).37 Yellow oil. H
1
NMR (400 MHz, CDCl3): δ 7.53 (d, JH−H = 8.1, 2H), 7.30 (d, JH−H
=
3-(Naphth-1-yl)cyclohexanone (5b).33 Yellow oil. H NMR (400
1
8.1, 2H), 2.95 (t, JH−H = 7.5, 2H), 2.78 (t, JH−H = 7.5, 2H), 2.15 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 207.5, 140.5, 128.1, 127.8,
125.7, 44.7, 29.6, 29.3. MS: m/z (%) 216 (100) [M+], 197 (21), 1173
(37), 159 (40), 153 (18),133 (23), 109 (12).
MHz, CDCl3): δ 8.03 (d, JH−H = 8.0, 1H), 7.87−7.85 (m, 1H), 7.54
(d, JH−H = 8.0, 1H), 7.54−7−47 (m, 4H), 3.9−3.8 (m, 1H), 2.89−2.39
(m, 4H), 2.30−2.10 (m, 2H), 2.04−1.82 (m, 2H). 13C NMR (100
MHz, CDCl3): δ 211.2, 139.9, 133.9, 130.8, 129.0, 127.2, 126.1, 125.6,
125.5, 122.6, 122.4, 48.5, 41.4, 39.3, 32.2, 25.5. MS: m/z (%) 224 (88)
[M+], 181 (17), 168 (17), 167 (100), 165 (26), 154 (36), 153 (53),
152 (40), 141 (25), 128 (12).
4-(4-Bromophenyl)butan-2-one (13d).38 Yellow oil. 1H NMR
(400 MHz, CDCl3): δ 7.38 (d, JH−H = 8.3, 2H), 7.05 (d, JH−H = 8.3,
2H), 2.84 (t, JH−H = 7.2, 2H), 2.73 (t, JH−H = 7.2, 2H), 2.13 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 207.4, 139.9, 131.4, 130.0, 119.8,
44.7, 30.0, 29.0. MS: m/z (%) 228 (98) [M+ + 2], 226 (100) [M+],
213 (23), 211 (24), 185 (30), 183 (31), 171 (85), 169 (87), 147 (79),
132 (17), 104 (76), 103 (36), 102 (17), 90 (25), 89 (24), 78 (19), 77
(38).
3-[4-(Trifluoromethyl)phenyl]cyclohexanone (5c).34 Yellow oil. 1H
NMR (400 MHz, CDCl3): δ 7.06 (d, JH−H = 7.9, 2H), 7.34 (d, JH−H
=
7.9, 2H), 3.12−3.04 (m, 1H), 2.59−2.38 (m, 4H), 2.19−2.08 (m, 2H),
1.90−1.82 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 210.1, 150.5,
148.2, 127.0, 125.7, 77.2, 48.5, 44.5, 41.1, 32.5, 25.4. MS: m/z (%) 242
(54) [M+], 223 (12), 200 (11), 199 (100), 186 (34), 185 (18), 172
(41), 171 (13), 145 (13), 103 (13).
4-(4-Methoxyphenyl)butan-2-one (13e).36 Yellow oil. 1H NMR
(400 MHz, CDCl3): δ 7.10−7.08 (m, 2H), 6.82−6.80 (m, 2H), 3.77
(s, 3H), 2.83 (t, JH−H = 7.5, 2H), 2.71 (t, JH−H = 7.5, 2H), 2.12 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 208.0, 157.8, 132.9, 129.1, 133.8,
55.1, 45.3, 30.0, 28.8. MS: m/z (%) 178 (40) [M+], 121 (100), 91
(11).
3-(4-Bromophenyl)cyclohexanone (5d).35 Yellow oil. 1H NMR
(400 MHz, CDCl3): δ 7.47−7.43 (m, 2H), 7.12−7.07 (m, 2H), 3.01−
2.93 (m, 1H), 2.61−2.32 (m, 4H), 2.19−2.05 (m, 2H), 1.88−1.73 (m,
2H). 13C NMR (100 MHz, CDCl3): δ 207.4, 139.9, 131.4, 130.0,
119.8, 44.7, 30.0, 29.0. MS: m/z (%) 254 (98) [M+ + 2], 252 (100)
[M+], 209 (40), 198 (19), 197 (55), 196 (20), 195 (55), 184 (47), 183
(12), 182 (48), 173 (15), 171 (12), 145 (15), 117 (15), 116 (67), 115
(29), 103 (23), 102 (19), 77 (23).
Structural Analysis of Complex 2. Crystals suitable for X-ray
diffraction were obtained by slow diffusion of pentane into a
concentrated solution of 2 in dichloromethane. X-ray data were
collected on a Bruker Smart APEX CCD diffractometer equipped with
a normal-focus, 2.4 kW sealed-tube source (Mo radiation, λ = 0.710 73
Å) operating at 50 kV and 40 mA. Data were collected over the
complete sphere by a combination of four sets. Each frame exposure
time was 10 s, covering 0.3° in ω. Data were corrected for absorption
by using a multiscan method applied with the SADABS program.39
The structure was solved by Patterson (Rh atom) and conventional
Fourier techniques and refined by full-matrix least squares on F2 with
SHELXL97.40 Anisotropic parameters were used in the last cycles of
refinement for all non-hydrogen atoms. Hydrogen atoms (except those
corresponding to the olefinic carbon atoms and that of the OH, which
were observed in the difference Fourier maps and refined as free
isotropic atoms) were included in calculated positions and refined
riding on their respective carbon atoms with the thermal parameter
related to the bonded atoms. All the highest electronic residuals were
observed in the close proximity of the Rh center and make no
chemical sense.
3-(4-Methoxyphenyl)cyclohexanone (5e).32 Yellow oil. H NMR
1
(400 MHz, CDCl3): δ 7.20 (d, JH−H = 8.7, 2H), 6.93 (d, JH−H = 8.7,
2H), 3.85 (s, 3H), 3.09−2.97 (m, 1H), 2.62−2.42 (m, 4H), 2.23−2.09
(m, 2H), 1.90−1.82 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 211.1,
158.2, 136.5, 127.4, 113.9, 55.2, 49.2, 43.9, 41.1, 32.9, 25.4. MS: m/z
(%) 204 (63) [M+], 147 (100), 134 (31), 121 (16), 119 (12), 91 (19).
3-(o-Tolyl)cyclohexanone (5f).33 Yellow oil. H NMR (400 MHz,
1
CDCl3): δ 7.25−7.04 (m, 5H), 3.25−3.16 (m, 1H), 2.53−2.34 (m,
4H), 2.32 (s, 3H), 2.18−2.17 (m, 1H), 2.02−1.99 (m, 1H), 1.89−1.76
(m, 2H). 13C NMR (100 MHz, CDCl3): δ 211.3, 142.3, 135.1, 130.7,
126.5, 126.4, 125.1, 48.4, 41.3, 40.4, 32.0, 25.8, 19.3. MS: m/z (%) 188
(72) [M+], 173 (17), 146 (17), 145 (100), 132 (12), 131 (86), 129
(14), 118(43), 117 (55), 115 (34), 105 (24), 91 (31).
3-(3-Chlorophenyl)cyclohexanone (5g).33 Colorless oil. H NMR
1
(400 MHz, CDCl3): δ 7.38−7.24 (m, 4H), 3.07−2.99 (m, 1H), 2.69−
2.34 (m, 4H), 2.24−2.05 (m, 2H), 2.93−1.64 (m, 2H). 13C NMR
(100 MHz, CDCl3): δ 210.5, 146.2, 134.4, 129.9, 128.7, 126.9, 124.8,
48.6, 44.3, 41.0, 32.5, 25.4. MS: m/z (%) 208 (26) [M+ + 2], 210 (83)
[M+], 167 (35), 166 (13), 165 (100), 153 (15), 152 (28), 151 (37),
145(21), 140 (20), 139 (19), 138 (55), 129 (14), 125 (18), 117 (18),
116 (17), 115 (32), 103 (37), 102 (16), 101 (11), 77 (23).
3-Phenylcycloheptanone (11).33 Colorless oil. 1H NMR (400
MHz, CDCl3): δ 7.33−7.26 (m, 2H), 7.23−7.16 (m, 3H), 2.98−2.89
(m, 2H), 2.67−2.57 (m, 3H), 2.11−1.96 (m, 3H), 1.80−1.62 (m, 2H),
1.56−1.47 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 213.4, 146.9,
128.6, 126.4, 126.3, 51.2, 43.9, 42.7, 39.2, 29.2, 24.1. MS: m/z (%) 188
(100) [M+], 145 (13), 131 (62), 130 (60), 129 (24), 118 (16), 117
(42), 115 (24), 105 (20), 104 (90), 103 (22), 97 (18), 91 (51), 78
(17), 77 (17).
Crystal data for 2: C26H30ClN2ORh, mol wt 524.88, yellow, prism
(0.08 × 0.06 × 0.02), monoclinic, space group Cc, a = 13.521(6) Å, b
= 21.920(9) Å, c = 7.978(3) Å, α = 90.00°, β = 103.597(7)o, γ =
90.00°, V = 2298.3(17) Å3, Z = 4, Dcalcd = 1.517 g cm−3, F(000) =
1080, T = 100(2) K, μ = 0.880 mm−1, 13 163 measured reflections (2θ
= 3−58°, ω scans 0.3°), 5437 unique reflections (Rint = 0.1045),
minimum/maximum transmission factors 0.703/0.967, final agreement
factors R1 = 0.0564 (3320 observed reflections, I > 2σ(I)) and wR2 =
0.1037, 5437/2/286 data/restraints/parameters, GOF = 0.856, largest
peak and hole 0.975 and −1.008 e/Å3.
ASSOCIATED CONTENT
* Supporting Information
■
S
A CIF file giving positional and displacement parameters,
crystallographic data, and bond lengths and angles of
compound 2. This material is available free of charge via the
Internet at http://pubs.acs.org.
4-Phenylbutan-2-one (13a).32 White solid. Mp: 78−80 °C
(acetone). 1H NMR (400 MHz, CDCl3): δ 7.31−7.26 (m, 2H),
7.21−7.17 (m, 3H), 2.90 (dt, JH−H = 6.4, 2.4, 2H), 2.76 (d, JH−H = 8.2,
2.4, 2H), 2.99 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 207.5,
140.5, 128.1, 127.8, 125.7, 44.7, 29.6, 29.3. MS: m/z (%) 148 (100)
[M+], 133 (19), 105 (98), 91 (69), 79 (15), 78 (14), 77 (23), 65 (12),
51 (13).
AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
■
4-(Naphth-1-yl)butan-2-one (13b).36 Yellow oil. H NMR (400
1
MHz, CDCl3): δ 7.95 (d, JH−H = 8.1, 1H), 7.83−7.81 (m, 1H), 7.69
(d, JH−H = 8.1, 1H), 7.51−7.44 (m, 2H), 7.43−7.42 (m, 1H), 7.38−
7.28 (m, 1H),), 3.33 (t, JH−H = 7.5, 2H), 2.83 (t, JH−H = 7.5, 2H), 2.11
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 207.8, 136.9, 133.8, 131.5,
128.8, 126.8, 125.9, 125.8, 125.5, 123.3, 44.3, 29.9, 26.6. MS: m/z (%)
ACKNOWLEDGMENTS
Financial support from the Ministerio de Ciencia e Innovacion
(MICINN) of Spain (Projects CTQ2007-65218, CTQ2011-
23459, CTQ2011-24165, Consolider Ingenio 2010 CSD2007-
■
́
6159
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Article
Rodden, M.; Wilson, C. Chem. Commun. 2005, 1743. (c) Edworthy, I.
S.; Rodden, M.; Mungur, S. A.; Davis, K. M.; Blake, A. J.; Wilson, C.;
00006), the Generalitat Valenciana (PROMETEO/2009/0349
́ ́
and FEDER), the Diputacion General de Aragon (E35), and
the European Social Fund is acknowledged. I.P. thanks the
MICINN for a predoctoral fellowship.
Schroder, M.; Arnold, P. L. J. Organomet. Chem. 2005, 690, 5710.
̈
(d) Torregrosa, R.; Pastor, I. M.; Yus, M. Tetrahedron 2007, 63, 469.
(15) Of the 4427 structures of transition metals with NHC ligands
located in the Cambridge Structural Database, only 29 contain alcohol-
REFERENCES
functionalized imidazolylidene ligands: (a) Schwarz, J.; Bohm, V. P.
̈
■
W.; Gardiner, M. G.; Grosche, M.; Herrmann, W. A.; Hieringer, W.;
Raudaschl-Sieber, G. Chem. Eur. J. 2000, 6, 1773. (b) Glas, H.;
Herdtweck, E.; Spiegler, M.; Pleier, A.-K.; Thiel, W. R. J. Organomet.
Chem. 2001, 626, 100. (c) Melaiye, A.; Simons, R. S.; Milsted, A.;
Pingitore, F.; Wesdemiotis, C.; Tessier, C. A.; Youngs, W. J. J. Med.
(1) (a) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem.,
Int. Ed. 2007, 46, 2768. (b) Marion, N.; Nolan, S. P. Acc. Chem. Res.
2008, 41, 140. (c) Samojlowicz, C.; Bieniek, M.; Grela, K. Chem. Rev.
́
2009, 109, 3708. (d) Dıez-Gonzal
́
ez, S.; Marion, N.; Nolan, S. P.
Chem. Rev. 2009, 109, 3612.
Chem. 2004, 47, 973. (d) Pruhs, S.; Lehmann, C. W.; Furstner, A.
̈
̈
(2) Hindi, K. M.; Panzner, M. J.; Tessier, C. A.; Cannon, C. L.;
Youngs, W. J. Chem. Rev. 2009, 109, 3859.
(3) Mercs, L.; Albrecht, M. Chem. Soc. Rev. 2010, 39, 1903.
(4) (a) Arnold, P. L.; Pearson, S. Coord. Chem. Rev. 2007, 251, 596.
(b) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M. Chem.
Organometallics 2004, 23, 280. (e) Zarka, M. T.; Bortenschlager, M.;
Wurst, K.; Nuyken, O.; Weberskirch, R. Organometallics 2004, 23,
4817. (f) Melaiye, A.; Sun, Z.; Hindi, K.; Milsted, A.; Ely, D.; Reneker,
D. H.; Tessier, C. A.; Youngs, W. J. J. Am. Chem. Soc. 2005, 127, 2285.
(g) Ray, L.; Katiyar, C.; Raihan, M. J.; Nanavati, H.; Shaikh, M. M.;
Ghosh, P. Eur. J. Inorg. Chem. 2006, 3724. (h) Ray, L.; Katiyar, V.;
Barman, S.; Raihan, M. J.; Nanavati, H.; Shaikh, M. M.; Ghosh, P. J.
Organomet. Chem. 2007, 692, 4259. (i) Ray, L.; Shaikh, M. M.; Ghosh,
P. Dalton Trans. 2007, 4546. (j) Dominique, F. J.-B.; Gornitzka, H.;
Hemmert, C. J. Organomet. Chem. 2008, 693, 579. (k) Dominique, F.
J.-B.; Gornitzka, H.; Sournia-Saquet, A.; Hemmert, C. Dalton Trans.
2009, 340. (l) Arnold, P. L.; Sandford, M. S.; Pearson, S. M. J. Am.
Chem. Soc. 2009, 131, 13912. (m) Panzner, M. J.; Deeraksa, A.; Smith,
A.; Wright, B. D.; Hindi, K. M.; Kascatan-Nebioglu, A.; Torres, A. G.;
Judy, B. M.; Hovis, C. E.; Hilliard, J. K.; Mallett, R. J.; Cope, E.; Estes,
D. M.; Cannon, C. L.; Leid, J. G.; Youngs, W. J. Eur. J. Inorg. Chem.
Rev. 2009, 109, 3445. (c) de Frem
́
ont, P.; Marion, N.; Nolan, S. P.
Coord. Chem. Rev. 2009, 253, 862.
(5) (a) Herrmann, W. A.; Gooßen, L. J.; Spiegler, M. J. Organomet.
Chem. 1997, 547, 357. (b) McGuinness, D. S.; Cavell, K. J.
Organometallics 2000, 19, 741. (c) Ketz, B. E.; Cole, A. P.;
Waymouth, R. M. Organometallics 2004, 23, 2835. (d) Yu, X.-Y.;
Patrick, B. O.; James, B. R. Organometallics 2006, 25, 2359.
(6) (a) Grundemann, S.; Kovacevic, A.; Albrecht, M.; Faller, J. W.;
̈
Crabtree, R. H. Chem. Commun. 2001, 2274. (b) Kovacevic, A.;
Grundemann, S.; Miecznikowski, J. R.; Clot, E.; Eisenstein, O.;
̈
Crabtree, R. H. Chem. Commun. 2002, 2580. (c) Grundemann, S.;
̈
Kovacevic, A.; Albrecht, M.; Faller, J. W.; Crabtree, R. H. J. Am. Chem.
Soc. 2002, 124, 10473. (d) Appelhans, L. N.; Zuccaccia, D.; Kovacevic,
A.; Chianese, A. R.; Miecznikowski, J. R.; Macchioni, A.; Clot, E.;
Eisenstein, O.; Crabtree, R. H. J. Am. Chem. Soc. 2005, 127, 16299.
2009, 1739. (n) Jokic,
Herdtweck, E.; Herrmann, W. A.; Kuhn, F. E. Inorg. Chim. Acta 2010,
363, 4181. (o) Straubinger, C. S.; Jokic,
Herdtweck, E.; Herrmann, W. A.; Kuhn, F. E. J. Organomet. Chem.
2011, 696, 687. (p) Jokic,
Straubinger, C. S.; Bechlars, B.; Herrmann, W. A.; Kuhn, F. E. J. J.
Organomet. Chem. 2011, 696, 3900. (q) Meyer, A.; Unger, Y.; Poethig,
A.; Strassner, T. Organometallics 2011, 30, 2980. (r) Benítez, M.; Mas-
́
N. B.; Straubinger, C. S.; Goh, S. L. M.;
̈
́
N. B.; Hogerl, M. P.;
̈
(e) Baya, M.; Eguillor, B.; Esteruelas, M. A.; Olivan, M.; Onate, E.
́
̃
̈
Organometallics 2007, 26, 6556. (f) Benítez, L.; Puerta, M. C.; Valerga,
P. Organometallics 2012, 31, 2175.
́
N. B.; Zhang-Presse, M.; Goh, S. L. M.;
̈
(7) (a) Wang, R.; Zeng, Z.; Twamley, B.; Piekarski, M. M.; Shreeve, J.
M. Eur. J. Org. Chem. 2007, 655. (b) Lee, H. M.; Chiu, P. L.; Hu, C.-
H.; Lai, C.-L.; Chou, Y.-C. J. Organomet. Chem. 2005, 690, 403.
(8) (a) Arnold, P. L.; Mungur, S. A.; Blake, A. J.; Wilson, C. Angew.
Chem., Int. Ed. 2003, 42, 5981. (b) Spencer, L. P.; Winston, S.; Fryzuk,
M. D. Organometallics 2004, 23, 3372. (c) Bonnet, L. G.; Douthwaite,
R. E.; Hodgson, R.; Houghton, J.; Kariuki, B. M.; Simonovic, S. Dalton
Trans. 2004, 3528. (d) Jong, H.; Patrick, B. O.; Fryzuk, M. D. Can. J.
Chem. 2008, 86, 803.
(9) (a) Yang, C.; Lee, H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511.
(b) Lee, H. M.; Chiu, P. L.; Zeng, J. Y. Inorg. Chim. Acta 2004, 357,
4313.
(10) (a) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord. Chem.
Rev. 2004, 248, 2201. (b) Bullock, R. M. Chem. Eur. J. 2004, 10, 2366.
́
Marza, E.; Mata, J. E.; Peris, E. Chem. Eur. J. 2011, 17, 10453.
(16) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47,
3122.
(17) Eguillor, B.; Esteruelas, M. A.; Olivan
Organometallics 2008, 27, 445.
(18) Esteruelas, M. A.; Lahoz, F. J.; Lop
́
, M.; Puerta, M.
́
ez, J. A.; Oro, L. A.;
Schlunken, C.; Valero, C.; Werner, H. Organometallics 1992, 11, 2034.
̈
́
(19) Eguillor, B.; Esteruelas, M. A.; Garcıa-Raboso, J.; Olivan
́
, M.;
Onate, E.; Pastor, I. M.; Penafiel, I.; Yus, M. Organometallics 2011, 30,
1658.
̃
̃
́
(20) Penafiel, I.; Pastor, I. M.; Yus, M.; Esteruelas, M. A.; Olivan, M.;
̃
Onate, E. Eur. J. Org. Chem. 2011, 7174.
̃
(c) Samec, J. S. M.; Backvall, J. E.; Andersson, P. G.; Brandt, P. Chem.
̈
(21) See for example: (a) Alcarazo, A.; Roseblade, S. J.; Alonso, E.;
Soc. Rev. 2006, 35, 237. (d) Kubas, G. J. Chem. Rev. 2007, 107, 4152.
(e) Vignais, P. M.; Billoud, B. Chem. Rev. 2007, 107, 4206.
(f) Fontecilla-Camps, J. C.; Volbeda, A.; Cavazza, C.; Nicolet, Y.
Fernandez, R.; Alvarez, E.; Lahoz, F. J.; Lassaletta, J. M. J. Am. Chem.
́
Soc. 2004, 126, 13242. (b) Burling, S.; Mahon, M. F.; Reade, S. P.;
Whittlesey, M. K. Organometallics 2006, 25, 3761. (c) Yu, X.-Y.;
Patrick, B. O.; James, B. R. Organometallics 2006, 25, 2359.
(d) Khramov, D. M.; Lynch, V. M.; Bielawski, C. W. Organometallics
Chem. Rev. 2007, 107, 4273. (g) Bolano, T.; Castarlenas, R.;
̃
Esteruelas, M. A.; Onate, E. J. Am. Chem. Soc. 2007, 129, 8850.
̃
́
(h) Esteruelas, M. A.; Garcıa-Yebra, C.; Onate, E. Organometallics
̃
2007, 26, 6042. (e) Gom
Cole, A. P.; Wender, P. A.; Waymouth, R. M. Organometallics 2007,
26, 4541. (f) Turkmen, H.; Pape, T.; Hahn, F. E.; Cetinkaya, B.
́
ez, F. J.; Kamber, N. E.; Deschamps, N. M.;
2008, 27, 3029. (i) Miranda-Soto, V.; Grotjahn, D. B.; Cooksy, A. L.;
Golen, J. A.; Moore, C. E.; Rheingold, A. L. Angew. Chem., Int. Ed.
2011, 50, 631.
̧
̈
Organometallics 2008, 27, 571. (g) Nonnenmacher, M.; Kunz, D.;
Rominger, F. Organometallics 2008, 27, 1561. (h) Bittermann, A.;
(11) (a) Raewsky, O. A.; Schaper, K.-J. Eur. J. Med. Chem. 1998, 33,
799. (b) Clark, D. E.; Pickett, S. D. Drug Discov. Today 2000, 5, 49.
(c) Abraham, M. H.; Ibrahim, A.; Zissimos, A. M.; Zhao, Y. H.;
Comer, J.; Reynolds, D. P. Drug Discov. Today 2002, 7, 1056.
(12) (a) Aharoni, S. M. Macromolecules 1989, 22, 686. (b) Paleos, C.
M.; Tsiourvas, D. Liq. Crystal. 2011, 28, 1127.
Harter, P.; Herdtweck, E.; Hoffmann, S. D.; Herrmann, W. A. J.
̈
Organomet. Chem. 2008, 693, 2079. (i) Jimen
́ ́
ez, M. V.; Perez-
Torrente, J. J.; Bartolome, M. I.; Gierz, V.; Lahoz, F. J.; Oro, L. A.
́
Organometallics 2008, 27, 224. (j) Rubio, M.; Jellema, E.; Siegler, M.
A.; Spek, A. L.; Reek, J. N. H.; de Bruin, B. Dalton Trans. 2009, 8970.
(k) Li, J.; Stewart, I. C.; Grubbs, R. H. Organometallics 2010, 29, 3765.
(13) Pillai, C. K. S.; Sandhya, K. Y.; Sudha, J. D.; Saminathan, H.
Pramana J. Phys. 2003, 61, 417.
(l) Gulcemal, S.; Daran, J.-C.; C
365, 264.
̧
etinkaya, B. Inorg. Chim. Acta 2011,
(14) (a) Arnold, P. L.; Rodden, M.; Davies, K. M.; Scarisbrick, A. C.;
Blake, A. J.; Wilson, C. Chem. Commun. 2004, 1612. (b) Arnold, P. L.;
̈
6160
dx.doi.org/10.1021/om300498e | Organometallics 2012, 31, 6154−6161

Organometallics
Article
(22) Barrio, P.; Esteruelas, M. A.; Lledos
Organometallics 2004, 23, 3008.
́
, A.; Onate, E.; Tomas
̀
, J.
(39) Blessing, R. H. Acta Crystallogr. 1995, A51, 33. SADABS: Area-
detector absorption correction; Bruker-AXS, Madison, WI, 1996.
(40) SHELXTL Package v. 6.10; Bruker-AXS, Madison, WI, 2000.
Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.
̃
(23) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997,
16, 4229. (b) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.;
Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579. (c) Hayashi, T.;
Yamasaki, K. Chem. Rev. 2003, 103, 2829. (d) Itooka, R.; Iguchi, Y.;
Miyaura, N. J. Org. Chem. 2003, 68, 6000. (e) Biteau, J.-G.; Minnaard,
A. J.; Feringa, B. L. J. Org. Chem. 2003, 68, 9481. (f) Ma, Y.; Song, C.;
Ma, C.; Sun, Z.; Chai, Q.; Andrus, M. B. Angew. Chem., Int. Ed. 2003,
42, 5871. (g) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J.
Am. Chem. Soc. 2003, 125, 11508. (h) Boiteau, J.-G.; Imbos, R.;
Minnaard, A. J.; Feringa, B. L. Org. Lett. 2003, 5, 681. (i) Hayashi, T.
Pure Appl. Chem. 2004, 76, 465. (j) Chen, F.-X.; Kina, A.; Hayashi, T.
Org. Lett. 2006, 8, 341. (k) Kina, A.; Iwamura, H.; Hayashi, T. J. Am.
Chem. Soc. 2006, 128, 3904. (l) Shintani, R.; Hayashi, T. Aldrichim.
Acta 2009, 42, 31. (m) Korenaga, T.; Osaki, K.; Maenishi, R.; Sakai, T.
Org. Lett. 2009, 11, 2325. (n) Lukin, K.; Zhang, Q.; Leanna, M. R. J.
Org. Chem. 2009, 74, 929. (o) Korenaga, T.; Maenishi, R.; Hayashi, K.;
Sakai, T. Adv. Synth. Catal. 2010, 352, 3247. (p) Berhal, F.; Esseiva, O.;
Martin, C.-H.; Tone, H.; Genet, J.-P.; Ayad, T.; Ratovelomanana-Vidal,
V. Org. Lett. 2011, 13, 2806.
(24) (a) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J.
Am. Chem. Soc. 2002, 124, 5052. (b) Fagnou, K.; Lautens, M. Chem.
Rev. 2003, 103, 169. (c) Truscott, B. J.; Fortman, G. C.; Slawin, A. M.
Z.; Nolan, S. P. Org. Biomol. Chem. 2011, 9, 7038.
(25) The first optimization process was performed by using a design
of experiments approach: (a) Chen, J. J.; Nugent, T. C.; Lu, C. V.;
Kondapally, S.; Giannousis, P.; Wang, Y.; Wilmot, J. T. Org. Process
Res. Dev. 2003, 7, 313. (b) Aggarwal, V. K.; Staubitz, A. C.; Owen, M.
Org. Process Res. Dev. 2006, 10, 64. (c) Veum, L.; Pereira, S. R. M.; van
der Waal, J. C.; Hanefeld, U. Eur. J. Org. Chem. 2006, 1664.
(d) Denmark, S. E.; Butler, C. R. J. Am. Chem. Soc. 2008, 130, 3690.
(e) Kuethe, J. T.; Tellers, D. M.; Weissman, S. A.; Yasuda, N. Org.
́
Process Res. Dev. 2009, 13, 471. (f) Mendiola, J.; Garcıa-Cerrada, S.; de
́
Frutos, O.; de la Puente, M. L.; Gu, R. L.; Khau, V. V. Org. Process Res.
Dev. 2009, 13, 292. (g) Massari, L.; Panelli, L.; Hughes, M.; Stazi, F.;
Maton, W.; Westerduin, P.; Scaravelli, F.; Bacchi, S. Org. Process Res.
Dev. 2010, 14, 1364. (h) Mateos, C.; Mendiola, J.; Carpintero, M.;
Mínguez, J. M. Org. Lett. 2010, 12, 4924. (i) Mathiessen, B.; Jensen, A.
T. I.; Zhuravlev, F. Chem. Eur. J. 2011, 17, 7796.
(26) Phenylboronic acid could provide water to the reaction through
a dehydration equilibrium with triphenylboroxine.
(27) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Miyaura, N. In Metal-Catalyzed Cross-Coupling Reactions; Wiley:
New York, 2004; p 41.
(28) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem. Soc. 2007,
129, 1876.
(29) (a) Trost, B. M.; Kulawiec, R. J. J. Am. Chem. Soc. 1993, 115,
2027. (b) Uma, R.; Crev
(c) Esteruelas, M. A.; Hernan
Onate, E. Organometallics 2005, 24, 5989. (d) Martın-Matute, B.;
́
isy, C.; Gree
́
, R. Chem. Rev. 2003, 103, 27.
́
dez, Y. A.; Lop
́
ez, A. M.; Olivan, M.;
́
́
̃
Bogar
́
, K.; Edin, M.; Kaynak, F. B.; Backvall, J. E. Chem. Eur. J. 2005,
11, 5832. (e) Batuecas, M.; Esteruelas, M. A.; Garcıa-Yebra, C.; Onate,
E. Organometallics 2010, 29, 2166.
̈
́
̃
(30) Holleck, L.; Mahapatra, S. Monatsh. Chem. 1969, 100, 1928.
́
(31) Uson, R.; Oro, L. A.; Cabeza, J. A. Inorg. Synth. 1985, 23, 126.
(32) Lu, X.; Lin, S. J. Org. Chem. 2005, 70, 9651.
(33) Chen, J.; Chen, J.; Lang, F.; Zhang, X.; Cun, L.; Zhu, J.; Deng, J.;
Liao, J. J. Am. Chem. Soc. 2010, 132, 4452.
(34) Jana, R.; Tunge, J. A. J. Org. Chem. 2011, 76, 8376.
(35) Nakao, Y.; Chen, J.; Imanaka, H.; Hiyama, T.; Ichikawa, Y.;
Duan, W.-L.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129,
9137.
(36) Li, X.; Li, L.; Tang, Y.; Zhong, L.; Cun, L.; Zhu, J.; Liao, J.;
Deng, J. J. Org. Chem. 2010, 75, 2981.
(37) Condon, S.; Dupre,
Chem. 2002, 105.
́ ́ ́
D.; Falgayrac, G.; Nedelec, J.-Y. Eur. J. Org.
(38) Saito, T.; Nishimoto, Y.; Yasuda, M.; Baba, A. J. Org. Chem.
2007, 72, 8588.
6161
dx.doi.org/10.1021/om300498e | Organometallics 2012, 31, 6154−6161